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Single-Cell Transcriptomics Characterizes Cell Types in the Subventricular Zone and Uncovers Molecular Defects Underlying Impaired Adult Neurogenesis

49 Pages Posted: 27 Jul 2018 Sneak Peek Status: Review Complete

See all articles by Vera Zywitza

Vera Zywitza

Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine

Aristotelis Misios

Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine

Lena Bunatyan

Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine

Thomas E. Willnow

Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine

Nikolaus Rajewsky

Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine

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Abstract

Neural stem cells (NSCs) contribute to plasticity and repair of the adult brain. Niches harboring NSCs are crucial for regulating stem cell self-renewal and differentiation. We used single-cell RNA profiling to generate an unbiased molecular atlas of all cell types in the largest neurogenic niche of the adult mouse brain, the subventricular zone (SVZ). We characterized > 20 neural and non-neural cell types and gained insights into the dynamics of neurogenesis by predicting future cell states based on computational analysis of RNA kinetics. Furthermore, we apply our single-cell approach to mice lacking LRP2, an endocytic receptor required for SVZ maintenance. The number of NSCs and proliferating progenitors was significantly reduced. Moreover, Wnt and BMP4 signaling was perturbed. We provide a valuable resource for adult neurogenesis, insights into SVZ neurogenesis regulation by LRP2, and a proof-of-principle demonstrating the power of single-cell RNA-seq in pinpointing neural cell type-specific functions in loss-of-function models.

Suggested Citation

Zywitza, Vera and Misios, Aristotelis and Bunatyan, Lena and Willnow, Thomas E. and Rajewsky, Nikolaus, Single-Cell Transcriptomics Characterizes Cell Types in the Subventricular Zone and Uncovers Molecular Defects Underlying Impaired Adult Neurogenesis (2018). Available at SSRN: https://ssrn.com/abstract=3219929 or http://dx.doi.org/10.2139/ssrn.3219929
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Vera Zywitza (Contact Author)

Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine ( email )

Robert Rössle Str 10
Berlin, 10178
Germany

Aristotelis Misios

Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine

Robert Rössle Str 10
Berlin, 10178
Germany

Lena Bunatyan

Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine

Anna-Louisa-Karsch-Straße 2
Berlin, 10178
Germany

Thomas E. Willnow

Molecular Cardiovascular Research, Max Delbrück Center for Molecular Medicine

Anna-Louisa-Karsch-Straße 2
Berlin, 10178
Germany

Nikolaus Rajewsky

Laboratory for Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine ( email )

Robert Rössle Str 10
Berlin, 10178
Germany

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